The compound known under the generic name omeprazole is disclosed in EP 0 005 129.
Omeprazole is useful for inhibiting gastric acid secretion and has gastric mucosa protective activity in mammals and man. Omeprazole may be used for prevention and treatment of gastric acid related disorders and gastrointestinal inflammatory diseases in mammals and man, including for example gastritis, gastric ulcer and duodenal ulcer.
S-omeprazole magnesium, the generic name for magnesium bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole), is a well-known gastric proton-pump inhibitor and has been commercially available from AstraZeneca under the brand name NEXIUM since 2001.
Certain salts of omeprazole are disclosed in EP 0 124 495. Canadian patent 2166794 disclosed a form of magnesium omeprazole dihydrate, which has a higher degree of crystallinity. This form has a methanol content of less than 0.1%.
Canadian patent application No. 2254572 discloses a process for the production of magnesium omeprazole crystalline dihydrate.
WO 97/41114 describes a procedure for preparing omeprazole magnesium and S-omeprazole magnesium with a low content of inorganic impurities.
EP 1 230 237 describes a procedure of removing residual solvents in omeprazole magnesium and EP 1 375 497 a procedure of removing residual solvents in S-omeprazole magnesium by flash evaporation but the products have unrepeatable low crystallinity between amorphous and a degree of crystallinity around 25% and still contain various amounts of residual solvents.
One enantiomer of omeprazole was prepared by separation of diastereoisomeric mixtures of derivatized omeprazole with further conversion to an enantiomer isolated as a syrupous substance in WO 92/08716.
A more convenient procedure for preparation of single isomer was done by chiral oxidation of a starting sulphide by cumene peroxide in the presence of titanium catalyst, diethyl tartrate and a base. The process is disclosed in WO 96/02535. The enantioselectivity of the foregoing transformation was high but there was still a need for removing residual R-enantiomer and overoxidation products like sulfones.
WO 97/02261 describes a method of further enrichment of S-enantiomer of omeprazole from already partially enriched mixtures by precipitating the racemate in selected solvents.
WO 96/17077 describes enzymatic enantioresolution of omeprazole and an analytical HPLC procedure of enantiomer determination.
WO 03/008406 describes a procedure of removing overoxidation products from S-enantiomer of omeprazole by extraction of S-enantiomer of omeprazole with water solution having selected pH values.
WO 94/27988 describes a solid form of S-omeprazole magnesium.
WO 95/01977 describes solid omeprazole magnesium with a degree of crystallinity over 70%.
WO 98/54171 describes a magnesium salt of S-omeprazole trihydrate characterized by being highly crystalline and stable. It discloses also polymorphic forms (A and B) of S-omeprazole magnesium salt dihydrate and processes for their preparation using S-omeprazole potassium salt as an intermediate.
WO 04/020436 discloses amorphous S-omeprazole magnesium salt in a hydrate form.
WO 04/046134 describes a crystalline S-omeprazole magnesium salt trihydrate form II wherein the term trihydrate is used to define a crystalline material in which water molecules are bound in the crystalline lattice.
WO 03/051867 describes separating omeprazole enantiomers by using simulated moving bed chromatography. Separation requires using technologically demanding procedures of chiral column chromatography to provide enantioresolution of 2-pyridinylmethylsulfinyl-1H-benzimidazoles.
In light of the foregoing, the object of the present invention was to produce a salt of omeprazole or its S-enantiomer that has acceptably low levels of organic solvent and can be produced by a simple process.